Quality of the voice after injection of hyaluronic acid into the vocal fold

Background

Voice disorders resulting from glottic insufficiency are a common clinical problem in everyday phoniatric practice. Asthenic, breathy, weak voice, hoarseness and vocal fatigue are characteristics of this kind of dysfunction. A reduced dynamic range of the voice is also found. During phonation, hyperactivity of the laryngeal and neck muscles occurs as a result of compensation. Such voice disorders are the result of presbyphonia, unilateral vocal fold paralysis, glottic insufficiency in functional dysphonia, or vocal fold scar or sulcus.

Injection laryngoplasty is a treatment for glottic insufficiency. Vocal fold injection was first described by Brunings in 1911 [1] and implemented by Arnold in the 1960’s. When considering material for injection, one has to consider the following factors: availability, costs, tolerance by the patient, resistance to resorption, ease of use, and complete biocompatibility [2]. Over the last few decades surgeons have used various augmentation materials, including Teflon, bovine collagen, autologous collagen, homogenic collagen, calcium hydroxylapatite, and autologous fat. Recently, cross-linked hyaluronic acid became more popular in phonosurgery, as it does not induce any inflammatory responses in the vocal fold area. Hyaluronic acid is one of the natural components of Reinke’s space, and after injection provides viscoelasticity of the superficial layer of the lamina propria. It remains stable after injection into the vocal fold. Initial research indicated that hyaluronic acid attracts fibroblasts, which generate new collagen and extracellular matrix macromolecules, resulting in endogenous soft tissue augmentation [3–6].

This study assessed voice quality in patients who were surgically treated with injection of hyaluronic acid into the vocal fold.

Material and Methods

SURGICAL PROCEDURE:

Microsurgical procedures were performed under general anesthesia (jet ventilation) using suspension laryngoscopy. Surgiderm 24 XP hyaluronic acid (Allergan) was used for the injection. The augmentation was performed with a 25 gauge (0.5 mm) laryngeal needle as close to the deep layer of the lamina propria as possible.

In the case of unilateral vocal fold paralysis, the main injection must be made anteriorly to the vocal process. Further injections should be located laterally and medially. If filling of Reinke’s space is needed, injection should be at the mid-point of the vocal fold. In scar and sulcus vocalis, the procedure consisted of 2 stages. The first stage included CO2 laser-assisted dissection of the epithelium (Acuspot Micromanipulator, Sharplan) at the level of the adherent area. The second stage was hyaluronic acid augmentation to correct the deficit. In the case of bilateral sulcus, the injection was symmetrical. In other cases the location of the injection depended on individual indications. In patients with presbyphonia, glottic insufficiency, and vocal fold atrophy in functional dysphonia, the hyaluronic acid was injected into Reinke’s space, as close to the vocal ligament as possible, to correct the vocal fold volume and relocate the free edge to the midline. The amount of hyaluronic acid used depended on the indication and on the estimation of the glottic gap, and ranged between 0.2 and 0.8 ml per side [8,9].

In the postoperative period, antibiotics were administered for 6 days and the voice rested for 2 days, although patients with scars were given strict vocal rest for 8 days. The program of care after hyaluronic acid augmentation was provided by the Audiology and Phoniatrics Clinic of the Institute of Physiology and Pathology of Hearing. After the operation, patients were included in a voice rehabilitation program for 3 months (1 visit per week) [10].

Results

After the operation we obtained complete or almost complete glottic closure in all cases (Figures 1, 2). One month after the procedure, videostroboscopic examination revealed recurrence of vocal fold vibrations in 8 cases (6 patients with irregular and 2 patients with regular vibrations). After 3 months vocal fold vibrations occurred in 15 cases and after 6 months 23 cases were seen. Lack of vibrations at 6 months was observed in only 2 cases (a case of unilateral paralysis and a vocal fold scar). Videostroboscopic evaluation performed 1, 3, and 6 months after surgery did not show any significant resorption of hyaluronic acid in the vocal fold that could affect the shape and efficiency of the glottis.

The injection laryngoplasty method improved the patients’ perceptual voice quality, as assessed by the GRBAS scale. Every single parameter examined decreased in intensity (Table 2) over each period of postoperative observation (1, 3, and 6 months). The most significant improvement was obtained 1 month after surgery (p=0.0002). Over the next few months, further statistically important improvements (p=0.000002) were noted. Finally, voice stabilization was achieved. Differences in GRBAS parameters before and after surgery were statistically significant for each evaluated period. The largest differences were observed 6 months after augmentation (Figure 3). Analysis of single parameters showed that the best results were obtained with the G parameter (hoarseness) and B parameter (breathiness). The G parameter had improved after 1 month of follow-up (p=0.000044) and after 6 months the p-level was <10−7. The R parameter (roughness) significantly changed after 1 month postoperatively, and after 6 months the p level was 0.0002. The B parameter, which indirectly describes the degree of phonation closure, improved significantly during the first month after surgery (p≤10−5), and then stabilized after 6 months. The A parameter improved in all patients during the whole observation period, reaching the highest significance 3 months after surgery (p<10−6). The S parameter (strain) achieved the greatest improvement and stabilization 6 months after surgery (p=0.000056).

Voice acoustic examinations revealed improvements in the acoustic structure of the voice in all patients after injection (Table 3).

The most significant and rapid improvements were obtained within the group of frequency parameters, especially the vFo parameter (fundamental frequency variation), which before the surgery was 3.02% and 3 months after surgery was 2.21%, with a significance level of p=0.028. The other parameters describing frequency disorders reached statistically important improvement 3 and 6 months after surgery (Figures 4, 5).

All parameters describing amplitude perturbation, such as Shim, APQ, sAPQ, and vAm, showed statistically significant improvement after 6 months postoperatively.

In the group of parameters describing noise components, results improved over time. The most rapid statistically significant improvement (p=0.0016) was obtained 1 month after surgery in the soft phonation index (SPI). This parameter is a good indicator of the vocal fold adduction during phonation. An increased soft phonation index is characteristic of patients diagnosed with incomplete glottic closure. However, the NHR parameter (describing noise to harmonic ratio) and the voice turbulence index (VTI) showed gradual improvements but did not reach statistical significance. Stabilization of the noise parameter indexes confirmed improvement of vocal fold adduction and reduction of glottic gap after hyaluronic acid injection.

Discussion

The results obtained in the present study indicate that application of hyaluronic acid augmentation to the vocal fold in cases having insufficient glottic closure provides good and very good voice quality and speeds rehabilitation of the voice. Satisfactory glottic closure was obtained after surgery in all cases. The satisfactory outcomes were confirmed by videostroboscopic assessment and objective acoustic examination of the voice. The patients selected for this surgical treatment had reported voice disorders of about 2 years duration. All patients had a medical history of attempts at phoniatric rehabilitation without satisfactory voice quality improvement. As recommended by a range of clinical centers, the patients were told to rest their voice in the postoperative period and were given voice therapy for 3 months after the surgery [8].

The study group showed immediate improvement in voice quality after the treatment, although better results were achieved after 3 months. After 6 months, full stabilization of voice had occurred, and this was statistically significant, as well as being noticeable to the patients themselves. In perceptual assessment of the voice, all parameters improved after surgery, but only in 3 cases was hoarseness (described by the G parameter) totally eliminated. We attribute this to bad habits and abnormal voice production. Both were present and escalated in the preoperative period; they ultimately had an impact on the final outcome. For most of the patients, this functional factor was at work during the whole follow-up period, and as a compensational mechanism it affected the treatment. In a few cases it prevented satisfactory voice outcomes. The most difficult group was those patients with coexisting ventricular dysphonia. The best postoperative voice outcomes were noted in patients with unilateral vocal fold paralysis, which is consistent with literature reports [9,11,12]. The criteria for patient selection for surgery should verify that there is a coexisting functional change within the vocal pathway. Some authors note that the best results are obtained in cases of a phonatory gap smaller than 3 mm [2]. Our previous experience indicates that the size of the phonatory gap is a significant factor, but localization of the gap is also important. In the presented material, a return of vibratory movement in patients with oval glottic gap (maximum opening in the middle part of the glottis) was seen first.

During the whole 8-month follow-up period, no adverse inflammatory reactions within vocal folds or laryngeal structures were found. There were no signs of hyaluronic acid resorption or voice deterioration. Interestingly, the opposite effect was seen: month by month, the patients’ voices became more stable and normal within the acoustic structure. The literature indicates that hyaluronic acid injected into Reinke’s space has the ability to stimulate growth of new connective tissue – collagen, fibroblasts, and hyaluronic acid – providing long-term filling and elasticity of the vocal fold [13]. In comparison to other implantable materials such as autologous fat, Teflon, collagen, or calcium hydroxylapatite, hyaluronic acid seems to be quite resistant to resorption [2,14,15]. As reported by other authors, resorption of hyaluronic acid takes about 6–12 months. Biocompatibility and resistance to resorption, ease of the injection method, and, above all, a long-term functional vocal result, proves that hyaluronic acid augmentation into the vocal fold is effective and safe.

Conclusions

In patients suffering from glottic insufficiency, injection of hyaluronic acid into the vocal fold significantly improves phonatory function of the larynx and quality of voice.

Augmentation of the vocal fold with hyaluronic acid is an effective and voice-improving method, restoring speech production. It may be a safe alternative to the conservative methods of treatment used in rehabilitation of voice disorders.

Hyaluronic acid injection to the vocal fold is an easy, effective, and fast method of restoring good voice quality.